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Prostate cancer (PCa) is an extremely common malignant tumor of the male genitourinary system, originating from the prostate gland epithelium. Male patients are prone to relapse after treatment, which seriously threatens their health. Phosphoinositide 3‐kinase (PI3K)/protein kinase B (PKB, also known as Akt) plays an important role in the growth, invasion, and metastasis of PCa. This review aimed to present an overview of the mechanism of action of the PI3K/AKT signaling pathway in PCa and discuss the application prospects of inhibitors of this pathway in treating PCa, providing a theoretical basis and reference for its clinical treatment targets. [ABSTRACT FROM AUTHOR]

In the rate‐state friction law framework, the transition from velocity weakening (V‐W) to velocity strengthening (V‐S) behavior marks the base of the seismogenic crust. Here we investigate the role of fault slip displacement under hydrothermal conditions in controlling the V‐W to V‐S transition. We shear simulated gabbro gouges at slip velocities ranging from 16 nm/s (∼50 cm/year) to 10 μm/s (∼8 cm/day) under hydrothermal conditions (300–400°C temperature; 30 MPa pore fluid pressure). We observe that cumulative fault slip increases the critical velocity for the V‐W to V‐S transition. The transition is accompanied by localized to distributed deformation mode, the formation of smectite‐type clays and occurrence of intergranular mass transfer. Our results provide insights into understanding the deepening and shallowing of V‐W/V‐S boundary (lower limit of the seismogenic zone) following a mainshock. Besides strain rate effects, slip‐enhanced chemical alteration and grain size‐sensitive deformation may temporarily contribute to the shallowing process. Plain Language Summary: According to the standard model of earthquake nucleation, earthquakes are the result of frictional instabilities along faults. The necessary condition for earthquake nucleation is that the frictional strength of a fault decreases with fault slip velocity ("velocity‐weakening" behavior) or slip distance ("slip‐weakening" behavior). Although extensive laboratory studies have been conducted to investigate the velocity‐dependence of friction in rocks, less attention was paid to the role of slip displacement on fault frictional stability, especially in the presence of hot and pressurized fluids. The latter, difficult to reproduce in the laboratory, is a common condition at seismogenic depths. In this study, we examine how the frictional stability evolves with slip velocity and displacement on simulated faults made of powders of gabbro (a common rock of the oceanic crust) under hydrothermal conditions up to 400°C. We find that the critical velocity for the transition from velocity‐weakening to velocity‐strengthening increases with cumulative slip displacement. In nature, the increase of this critical velocity may result in the uplift, during seismic sequences, of the base of the seismogenic crust (i.e., aftershock hypocenters will be shallower). Our findings suggest that, slip displacement, accompanied by fault mineralogical‐structural evolution, can influence fault frictional stability and earthquake nucleation. Key Points: The role of slip displacement in controlling fault stability under hydrothermal conditions is investigatedThe critical velocity for transition in friction from velocity‐weakening to velocity‐strengthening increases with slip displacementThis frictional transition, attributed to chemical alteration, is accompanied by the transition from localized to delocalized deformation [ABSTRACT FROM AUTHOR]

This study investigates the crashworthiness of biomimetic composite thin‐walled tubes under quasi‐static axial crushing, focusing on the effects of geometric structure and fiber orientation. The thin‐walled tubes, inspired by honeycomb structures, were manufactured using carbon fiber composites through multi‐cavity preform mold method. Quasi‐static crushing tests and CT scanning observation were conducted to characterize the mechanical response, crashworthiness mechanisms and energy absorption capacity of the thin‐walled tubes. Results demonstrated excellent energy absorption capacities across all configurations, with the C‐0/45 configuration achieving the highest specific energy absorption at 115.03 kJ/kg. The optimal crushing energy absorption process for thin‐walled tubes involves achieving high peak loads and maintaining high load levels. Sustaining high loads requires progressive and stable damage without the formation of extensive intermediate cracks between different plies (indicative of strong interlaminar shear strength). The structural integrity of the uncrushed sections must remain intact without significant damage during the crushing process. Fiber orientation parallel to the loading direction enhances peak load levels and interlaminar shear strength between plies, but may compromise circumferential stiffness and structural stability. The influence of geometric configuration is primarily manifested in the progressive and stable crushing phase, where the tube requires sufficient space to accumulate its own debris without causing damage to the uncrushed thin‐walled structure. Highlights: Structures and fiber orientation boost crashworthiness in biomimetic composite tubes.Biomimetic structures were produced using a multi‐cavity preform mold method.CT scans were conducted to characterize the energy absorption mechanisms.Composite tubes demonstrated excellent energy absorption capacity of 115 kJ/kg. [ABSTRACT FROM AUTHOR]

Invasive pulmonary aspergillosis (IPA) is a life‐threatening complication in patients with severe fever with thrombocytopenia syndrome (SFTS), yet SFTS‐associated IPA (SAPA)'s risk factors remain undefined. A multicenter retrospective cohort study across Hubei and Anhui provinces (May 2013–September 2022) utilized least absolute shrinkage and selection operator (LASSO) regression for variable selection. Multivariable logistic regression identified independent predictors of SAPA, Cox regression highlighted mortality‐related risk factors. Of the 1775 screened SFTS patients, 1650 were included, with 169 developing IPA, leading to a 42‐day mortality rate of 26.6% among SAPA patients. Multivariable logistic regression revealed SAPA risk factors including advanced age, petechia, hemoptysis, tremor, low albumin levels, elongated activated partial thromboplastin time (APTT), intensive care unit (ICU) admission, glucocorticoid usage, intravenous immunoglobulin (IVIG) and prolonged hospital stays. Cox regression identified predictors of 42‐day mortality, including ecchymosis at venipuncture sites, absence of ICU admission, elongated prothrombin time (PT), vasopressor and glucocorticoid use, non‐antifungals. Nomograms constructed on these predictors registered concordance indexes of 0.855 (95% CI: 0.826–0.884) and 0.778 (95% CI: 0.702–0.854) for SAPA onset and 42‐day mortality, respectively. Lower survival rates for SAPA patients treated with glucocorticoids (p < 0.001) and improved 14‐day survival with antifungal therapy (p = 0.036). Improving IPA management in SFTS‐endemic areas is crucial, with effective predictive tool. [ABSTRACT FROM AUTHOR]

Background: Allergic diseases, including respiratory and food allergies, as well as allergic skin conditions have surged in prevalence in recent decades. In allergic diseases, the gut microbiome is dysbiotic, with reduced diversity of beneficial bacteria and increased abundance of potential pathogens. Research findings suggest that the microbiome, which is highly influenced by environmental and dietary factors, plays a central role in the development, progression, and severity of allergic diseases. The microbiome generates metabolites, which can regulate many of the host's cellular metabolic processes and host immune responses. Aims and Methods: Our goal is to provide a narrative and comprehensive literature review of the mechanisms through which microbial metabolites regulate host immune function and immune metabolism both in homeostasis and in the context of allergic diseases. Results and Discussion: We describe key microbial metabolites such as short‐chain fatty acids, amino acids, bile acids and polyamines, elucidating their mechanisms of action, cellular targets and their roles in regulating metabolism within innate and adaptive immune cells. Furthermore, we characterize the role of bacterial metabolites in the pathogenesis of allergic diseases including allergic asthma, atopic dermatitis and food allergy. Conclusion: Future research efforts should focus on investigating the physiological functions of microbiota‐derived metabolites to help develop new diagnostic and therapeutic interventions for allergic diseases. [ABSTRACT FROM AUTHOR]

The binary electron donor–electron acceptor (D‐A) type conjugated polymers have proven to be efficient dopant‐free hole‐transporting materials (HTMs) for the n‐i‐p perovskite solar cells (PVSCs). However, D‐A type terpolymeric HTMs containing two D units are not exploited. Reserving the high‐planarity backbone of benzodithiophene (BDT)‐benzodithiophene‐4,8‐dione, D1‐A‐D2‐A type terpolymers PT‐Cz30, PT‐Cz50, and PT‐Cz70 are obtained by side‐chain engineering and ternary copolymerization strategy, in which BDT bearing the side chains of thiophene and carbazole serves as D1 and D2 units, respectively. PT‐Cz50 performs best due to the appropriate side‐chain ratio around 1:1. Meanwhile, a polymer blend HTM PA‐Cz50 is studied for comparison, in which two binary D‐A polymers PBDB‐T and PBDB‐Cz are blended with the molar ratio of 1:1. Containing similar side‐chain composition, terpolymer PT‐Cz50 presents superior hole transport properties over the polymer blend PA‐Cz50 and endows better device performances to the PVSCs with a promising power conversion efficiency of 22.53% and high device stability. [ABSTRACT FROM AUTHOR]

Aims: We aim to explore the role and mechanism of vagus nerve stimulation (VNS) in coronary endothelial cells and angiogenesis in infarcted hearts. Methods and results: Seven days after rat myocardial infarction (MI) was prepared by ligation of the left anterior descending coronary artery, the left cervical vagus nerve was treated with electrical stimulation 1 h after intraperitoneal administration of the α7‐nicotinic acetylcholine inhibitor mecamylamine or the mAChR inhibitor atropine or 3 days after local injection of Ad‐shSDF‐1α into the infarcted heart. Cardiac tissue acetylcholine (ACh) and serum ACh, tumour necrosis factor α (TNF‐α), interleukin 1β (IL‐1β) and interleukin 6 (IL‐6) levels were detected by ELISA to determine whether VNS was successful. An inflammatory injury model in human coronary artery endothelial cells (HCAECs) was established by lipopolysaccharide and identified by evaluating TNF‐α, IL‐1β and IL‐6 levels and tube formation. Immunohistochemistry staining was performed to evaluate CD31‐positive vessel density and stromal cell‐derived factor‐l alpha (SDF‐1α) expression in the MI heart in vivo and the expression and distribution of SDF‐1α, C‐X‐C motif chemokine receptor 4 and CXCR7 in HCAECs in vitro. Western blotting was used to detect the levels of SDF‐1α, V‐akt murine thymoma viral oncogene homolog (AKT), phosphorylated AKT (pAKT), specificity protein 1 (Sp1) and phosphorylation of Sp1 in HCAECs. Left ventricular performance, including left ventricular systolic pressure, left ventricular end‐diastolic pressure and rate of the rise and fall of ventricular pressure, should be evaluated 28 days after VNS treatment. VNS was successfully established for MI therapy with decreases in serum TNF‐α, IL‐1β and IL‐6 levels and increases in cardiac tissue and serum ACh levels, leading to increased SDF‐1α expression in coronary endothelial cells of MI hearts, triggering angiogenesis of MI hearts with increased CD31‐positive vessel density, which was abolished by the m/nAChR inhibitors mecamylamine and atropine or knockdown of SDF‐1α by shRNA. ACh promoted SDF‐1α expression and its distribution along with the branch of the formed tube in HCAECs, resulting in an increase in the number of tubes formed in HCAECs. ACh increased the levels of pAKT and phosphorylation of Sp1 in HCAECs, resulting in inducing SDF‐1α expression, and the specific effects could be abolished by mecamylamine, atropine, the PI3K/AKT blocker wortmannin or the Sp1 blocker mithramycin. Functionally, VNS improved left ventricular performance, which could be abolished by Ad‐shSDF‐1α. Conclusions: VNS promoted angiogenesis to repair the infarcted heart by inducing SDF‐1α expression and redistribution along new branches during angiogenesis, which was associated with the m/nAChR‐AKT‐Sp1 signalling pathway. [ABSTRACT FROM AUTHOR]

Graphite is considered as a material that promotes fault weakening and electrical conductivity (σ) enhancement at fault zones. We studied how shear deformation may affect the evolution of friction and electrical conductivity of synthetic quartz (Qz)‐graphite (Gr) mixtures and, more importantly, whether the σ of the mixtures present visible changes at the beginning of the simulated fault slip. Long‐displacement friction experiments were performed on 1.2–2.3 mm‐thick gouge specimens of varied Gr volume fraction (XGr = 0–100 vol.%) under identical normal stress (2 or 5 MPa), slip rate (∼1.0 mm/s), and N2‐flushing conditions. The experimental results suggested that the σ of the specimens with ≥4.6 vol.% XGr abruptly increased under limited shear displacement. With continued shear, the steady‐state electrical conductivity (σss) increased by more than seven orders of magnitude when XGr > 3.4 vol.%, while the steady‐state frictional coefficient remained high (0.54–0.80) except for the specimens with XGr > 13.6 vol.%. The post‐mortem microstructures revealed that the high σss observed in the intermediate Gr content specimens (3.4–13.6 vol.%) is associated with an ad‐hoc fabric (graphite–cortex clasts) present in the principal slip zone. For high Gr content, excess Gr flakes fill the pores and help develop mechanically lubricated surfaces. We propose that low Gr content (i.e., as low as 3.4 vol.%) can cause high conductivity anomalies in natural shear zones. Overall, the findings suggest that the initiation of slips within carbonaceous shear zones can be detected by identifying unusual temporal signals using electromagnetic stations. Plain Language Summary: Crystalline graphite (Gr) can be enriched within fault zones due to mechanical or chemical processes and is considered a material that promotes fault weakening and electrical conductivity enhancement at fault zones. Geophysical observations suggest highly conductive anomalies in the carbonaceous shear zones and low apparent resistivity anomalies prior to an earthquake. Given this, we designed a novel experimental assembly to conduct electrical conductivity measurements on Gr‐bearing fault rocks along a fault‐parallel direction during a progressive fault slip in the laboratory. Our results revealed notably enhanced electrical conductivity under limited shear displacement, corresponding to the beginning of the simulated fault slip. With continued shear, the steady‐state electrical conductivity increases by more than seven orders of magnitude as the Gr content exceeds 3.4 vol.%, while the steady‐state frictional coefficient remains high until the Gr content exceeds 13.6 vol.%. Our results demonstrate that interconnected Gr networks are one of the main mechanisms that can explain high conductivity anomalies at shear zones and facilitate the detection of initiated slips in carbonaceous shear zones using electromagnetic stations. Key Points: Experiments work shows that the presence of graphite can cause abrupt increase in electrical conductivity at limited shear displacementGraphite–cortex clasts develop in the strain‐localized zoneInitiated slips at carbonaceous shear zones can be detected by monitoring temporal electromagnetic anomalies [ABSTRACT FROM AUTHOR]

Moderate eg filling for octahedral metal cations (MOh) is strongly correlated with the electrocatalytic water oxidation performance in the oxides system. Here, the eg fillings of NiOh and FeOh in NiFe2O4‐based spinel are controllably regulated by introducing an external radical of catalytically inactive MoSx as an electron acceptor via a novel ultrasonic anchored pyrolysis strategy. The electron occupied in eg orbit of MOh emigrates with the amount of MoS hanging on the apical of octahedral sites, and results in a salutary transition from high to medium eg occupancy state, as confirmed by the X‐ray absorption spectroscopy and X‐ray photoelectron spectroscopy. In addition, benefiting from the abundant unsaturated S atoms in amorphous MoSx, the MOh at the surface furthest activates and consequently shows a superior water oxidation performance. Density functional theory also reveals that the eg fillings of Ni and Fe decrease to 1.4 and 1.2 after MoSx modification, which can effectively reduce the free energy of the OOH* intermediates in the oxygen evolution reaction process. This work opens an avenue for further releasing the electrocatalytic activity of octahedral sites through bridging external phases with rational electron‐capturing/donating capability. [ABSTRACT FROM AUTHOR]

The intercalation of protons represents a notable component for energy storage in aqueous zinc‐ion batteries. However, the mechanism of proton transport in metal oxide cathodes, especially related to how the cation distribution modulates the proton‐conducting lanes, remains far from consensus due to the lack of suitable model materials. Here, taking spinel ZnMn2O4 cathode as a prototype, it is disclosed that a deficiency of one half of lattice Zn ions can triple its specific capacity at high rates, which is predominantly contributed by proton storage. This promotion can be rationalized by the emergence of facile concerted proton transport in the Zn‐deficient sample, contrasting with the stoichiometric one, where proton intercalation undergoes a slow consecutive process. Furthermore, the restricted Zn motion in spinel phase causes high structural stability during cycling, preventing the recombination of external Zn ions with Zn vacant sites that readily accommodate protons. This work highlights the key role of controlled off‐stoichiometry in optimizing proton transport and storage for aqueous batteries. [ABSTRACT FROM AUTHOR]

Buildings near direct current transmission lines are sensitive to the electromagnetic environment, and the measurement of the electric field above them is important in engineering design and environmental assessment in China. The models of buildings and probes in the ion flow field were established to explore the accurate measurement method of the electric field above the building. Based on the upstream finite element method and the predictor–corrector method, the influence of whether the probe was grounded or not above the building was studied. On this basis, simulation experiments and real‐type experiments were carried out. The results show that when the electrical conductivity of the building was greater than 10−10 S/m, being grounded or not would not change the results. When the building conductivity was between 10−11 and 10−12 S/m, the electric field measurement results would be increased by 30% to 120% after grounding. In the real‐type experiments on the platform with a plywood roof, the relative error in the electric field when grounded or not was only 2.6%. This proved the reliability of the calculated results. In this paper, the measuring method of the DC space charge‐modified electric field above buildings was analyzed first, and the conclusion that ground wire can be cancelled above buildings with general materials was presented. The research results can provide a technical basis for the accurate measurement of the electric field above the buildings near DC transmission lines. [ABSTRACT FROM AUTHOR]

Regenerated silk fibroin (RSF) fibers have great application prospects in medicine, textiles, optoelectronics, and other fields. However, under the synergistic action of ultraviolet, oxygen, and water, RSF will inevitably become brittle, which will greatly shorten the service life of RSF. Therefore, it is urgent to find some methods to protect RSF from aging damage. Cerium dioxide nanoparticles have a strong ultraviolet absorption and antioxidant capacity and have been used as an anti‐aging component for other biomaterials. Thus, the RSF/CeO2 NPs hybrid fibers were successfully prepared, and a series of artificial aging tests were carried out. Mechanical property is an important index to measure the aging degree. After aging, compared with RSF, the stress of RSF/CeO2 NPs hybrid fibers was increased by 130.47 ± 4.78 MPa, and the strain of RSF/CeO2 NPs hybrid fibers was increased by 69.89% ± 1.37%. The results of Fourier transform infrared spectroscopy, UV–Vis, sodium dodecyl sulfate polyacrylamide gel electrophoresis discussed the protective mechanism of CeO2 NPs, which prevent the transition from β‐sheet to α‐helix/random coil and the disorder of structure. Furthermore, RSF/CeO2 NPs hybrid fibers have an excellent antibacterial activity against Escherichia coli and Staphylococcus aureus bacteria; the antioxidant activity of RSF/CeO2 NPs hybrid fibers is gradually enhanced in the presence of UV‐light. [ABSTRACT FROM AUTHOR]

Control of droplet sliding and its interfacial behavior such as sliding resistance and friction have important applications in microfluidic and energy-related fields. Nature provides many examples of interface-driven droplet sliding control; yet, to date, the continuous governing of the multiphase process and precise steering of droplet sliding remain challenging. Here, directional-dependent ultraslippery patterned surfaces with significant droplet sliding anisotropy were created by coordinating the heterogeneous wettability of the back of the dessert beetle, directionaldependent architecture of the butterfly wing, and ultraslippery configuration of the Nepenthes alata. Analysis of the sliding resistance on typical ultraslippery patterned surfaces reveals that the directional-dependent triple phase line (TPL) immigration on the ultraslippery patterns dominates the strong sliding anisotropy, which can be modeled using the classic Furmidge equation. In particular, the sliding anisotropy for the semicircular ultraslippery patterned surface shows threefold higher than that of natural butterfly wings due to the most significant difference in TPL immigration in two opposite directions, which enables the simultaneous handling of multiple droplets without mass loss and steering of droplet sliding/friction. This work may transform the design space for the control of multiphase interface motion and the development of new lab-on-a-chip and droplet-based microsystems. [ABSTRACT FROM AUTHOR]

Background and Aim: Immune‐mediated neuroinflammation has been proposed to underlie the loss of lower esophageal sphincter (LES) myenteric neurons in achalasia. However, the immune status and key pathogenic immune subpopulations remain unclear. This study aims to evaluate the inflammatory status of patients with achalasia and their correlation with clinical characteristics, and further explore the key pathogenic subpopulations. Methods: We investigated the complete blood cell count and inflammatory markers in a large population of patients with achalasia (n = 341) and healthy controls (n = 80). The subpopulations of lymphocytes were analyzed by flow cytometry. Immunofluorescence was used to determine immune cell infiltration in the LES. Transcriptome changes of the key subpopulation were determined by RNA sequencing analysis. Results: NLR, MLR, CRP, globulin, IL‐6 and IL‐10 were significantly elevated in patients with achalasia. MLR and globulin were positively correlated with disease duration. The absolute count and percentage of CD8+ T cells in peripheral blood and its infiltration around ganglion in the LES were significantly increased in achalasia. Transcriptome analysis indicated that CD8+ T cells were activated and proliferative. In addition to multiple inflammatory pathways, regulation of neuroinflammatory response pathway was also significantly up‐regulated in achalasia. GSEA analysis revealed a close association with autoimmune diseases. Conclusions: Patients with achalasia suffered from chronic low‐grade inflammation with dysregulated immune cells and mediators associated with disease duration. CD8+ T cells might be the key pathogenic subpopulation of achalasia. Our results provide an important immune cell signature of the pathogenesis of achalasia. [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) for anastomotic lesions is technically challenging. We aimed to characterize the clinicopathologic characteristics, feasibility, and effectiveness of ESD for anastomotic lesions of the lower gastrointestinal tract. Method: We retrospectively investigated 55 patients with anastomotic lesions of the lower gastrointestinal tract who underwent ESD from February 2008 to January 2021. The lesions involving one or both sides of anastomoses were classified into the unilaterally involving anastomosis (UIA) or straddling anastomosis (SA) group, respectively. We collected clinicopathological characteristics, procedure‐related parameters and outcomes, and follow‐up data and analyzed the impact of anastomotic involvement. Results: The mean age was 62.5 years, and the median procedure duration was 30 min. The rates of en bloc resection and R0 resection were 90.9% and 85.5%, respectively. Four patients (7.3%) experienced major adverse events (AEs). During a median follow‐up of 66 months (range 14–169), seven patients had local recurrence, and six patients had metastases. The 5‐year disease‐free survival and overall survival rates were 82.4% and 90.7%, respectively. The 5‐year disease ‐specific survival (DSS) rate was 93.3%. Compared with the UIA group, the SA group had significantly longer procedure duration, larger specimen, lower rates of en bloc resection and R0 resection, and shorter disease‐free survival (all P < 0.05). However, rates of AEs did not differ significantly between the two groups. Conclusions: The short‐term and long‐term outcomes of ESD for colorectal anastomotic lesions were favorable. Although with technically challenging, ESD could be performed safely and effectively for lesions at the anastomoses. [ABSTRACT FROM AUTHOR]

Purpose: Synthetic digital mammogram (SDM) is a 2D image generated from digital breast tomosynthesis (DBT) and used as a substitute for a full-field digital mammogram (FFDM) to reduce the radiation dose for breast cancer screening. The previous deep learning-based method used FFDM images as the ground truth, and trained a single neural network to directly generate SDM images with similar appearances (e.g., intensity distribution, textures) to the FFDM images. However, the FFDM image has a different texture pattern from DBT. The difference in texture pattern might make the training of the neural network unstable and result in high-intensity distortion, which makes it hard to decrease intensity distortion and increase perceptual similarity (e.g., generate similar textures) at the same time. Clinically, radiologists want to have a 2D synthesized image that feels like an FFDM image in vision and preserves local structures such as both mass and microcalcifications (MCs) in DBT because radiologists have been trained on reading FFDM images for a long time, while local structures are important for diagnosis. In this study, we proposed to use a deep convolutional neural network to learn the transformation to generate SDM from DBT. Method: To decrease intensity distortion and increase perceptual similarity, a multi-scale cascaded network (MSCN) is proposed to generate low-frequency structures (e.g., intensity distribution) and high-frequency structures (e.g., textures) separately. The MSCN consist of two cascaded sub-networks: the first sub-network is used to predict the low-frequency part of the FFDM image; the second sub-network is used to generate a full SDM image with textures similar to the FFDM image based on the prediction of the first sub-network. The meansquared error (MSE) objective function is used to train the first sub-network, termed low-frequency network, to generate a low-frequency SDM image. The gradient-guided generative adversarial network's objective function is to train the second sub-network, termed high-frequency network, to generate a full SDM image with textures similar to the FFDM image. Results: 1646 cases with FFDM and DBT were retrospectively collected from the Hologic Selenia system for training and validation dataset, and 145 cases with masses or MC clusters were independently collected from the Hologic Selenia system for testing dataset. For comparison, the baseline network has the same architecture as the high-frequency network and directly generates a full SDM image. Compared to the baseline method, the proposed MSCN improves the peak-to-noise ratio from 25.3 to 27.9 dB and improves the structural similarity from 0.703 to 0.724, and significantly increases the perceptual similarity. Conclusions: The proposed method can stabilize the training and generate SDM images with lower intensity distortion and higher perceptual similarity. [ABSTRACT FROM AUTHOR]

Aqueous zinc‐ion battery (AZB) is a promising candidate for next‐generation energy storage owing to inherent safety and low cost. However, AZBs are currently plagued by Zn dendrite growth and undesirable side‐reactions, leading to poor cycling stability and premature failure. To restrain the uncontrollable Zn growth, a unique separator is developed based on polyacrylonitrile/graphene oxide (abbreviated as PG) composite nanofibers, which contain abundance of zincophilicity functional groups to regulate the migration and distribution of Zn2+ ions in the separator. It is demonstrated that the cyano ligands on PG not only facilitate the dehydration of solvated Zn2+ ions prior to deposition, but also form fast lanes to enable homogenous scattering of deposition spots. Benefiting from these features, the PG separator offers a high ionic conductivity of 7.69 mS cm‐1 and a transference number of 0.74 for Zn2+. The Zn||Zn symmetrical cells with PG separators achieve an ultra‐stable cycle life over 13 000 h. Zn||Zn0.27V2O5 full batteries with PG separators retain 71.5% of the original capacity after 2800 cycles at a high current density of 2 A g‐1. This study offers future research directions toward the design of multifunctional separators to overcome the limits of Zn metal anode in AZBs. [ABSTRACT FROM AUTHOR]

Metabolic health and immune function are intimately connected via diet and the microbiota. Nearly 90% of all immune cells in the body are associated with the gastrointestinal tract and these immune cells are continuously exposed to a wide range of microbes and microbial‐derived compounds, with important systemic ramifications. Microbial dysbiosis has consistently been observed in patients with atopic dermatitis, food allergy and asthma and the molecular mechanisms linking changes in microbial populations with disease risk and disease endotypes are being intensively investigated. The discovery of novel bacterial metabolites that impact immune function is at the forefront of host‐microbe research. Co‐evolution of microbial communities within their hosts has resulted in intertwined metabolic pathways that affect physiological and pathological processes. However, recent dietary and lifestyle changes are thought to negatively influence interactions between microbes and their host. This review provides an overview of some of the critical metabolite‐receptor interactions that have been recently described, which may underpin the immunomodulatory effects of the microbiota, and are of relevance for allergy, asthma and infectious diseases. [ABSTRACT FROM AUTHOR]

The ginsenoside Rg3 found in Panax species has extensive pharmacological properties, in particular anti‐cancer effects. However, its natural yield in Panax plants is limited. Here, we report a multi‐modular strategy to improve yields of Rg3 in a Panax ginseng chassis, combining engineering of triterpene metabolism and overexpression of a lignin biosynthesis gene, phenylalanine ammonia lyase (PAL). We first performed semi‐rational design and site mutagenesis to improve the enzymatic efficiency of Pq3‐O‐UGT2, a glycosyltransferase that directly catalyzes the biosynthesis of Rg3 from Rh2. Next, we used clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9) gene editing to knock down the branch pathway of protopanaxatriol‐type ginsenoside biosynthesis to enhance the metabolic flux of the protopanaxadiol‐type ginsenoside Rg3. Overexpression of PAL accelerated the formation of the xylem structure, significantly improving ginsenoside Rg3 accumulation (to 6.19‐fold higher than in the control). We combined overexpression of the ginsenoside aglycon synthetic genes squalene epoxidase, Pq3‐O‐UGT2, and PAL with CRISPR/Cas9‐based knockdown of CYP716A53v2 to improve ginsenoside Rg3 accumulation. Finally, we produced ginsenoside Rg3 at a yield of 83.6 mg/L in a shake flask (7.0 mg/g dry weight, 21.12‐fold higher than with wild‐type cultures). The high‐production system established in this study could be a potential platform to produce the ginsenoside Rg3 commercially for pharmaceutical use. [ABSTRACT FROM AUTHOR]

Riparian zones, an aquatic‐terrestrial interface, can intercept more than half of nitrogen (N) exported from terrestrial ecosystems to adjacent rivers, primarily by denitrification processes. However, damming has disrupted natural patterns and processes of flooding and vegetation community assemblages, and yet little is known about how hydrological changes and ecosystem restoration affect the biogeochemical functioning in the riparian ecosystems.We conducted an in situ experiment to evaluate the effects of hydrological change (e.g. altering flooding intensity and frequency) and restoration approaches (e.g. natural regeneration and active revegetation) on denitrification rates and the abundance of denitrifier genes in the riparian zone of the Three Gorges Reservoir, China.Our results showed that active revegetation did not significantly increase denitrification rates compared to the natural regeneration, but their underlying mechanism was different. At the natural regeneration area, the denitrification rate was primarily regulated by soil properties and abundance of nosZ gene, while at the active revegetation area, it was controlled merely by the abundance of nosZ gene. In addition, vegetation types showed little effect on the soil denitrification process, and the denitrification rate decreased with flooding intensity by reducing denitrifier gene abundance.The periodic flooding treatment doubled the denitrification rate compared with the no flooding treatment, which might be attributed to the enhancement of soil carbon availability. Our results suggest that in terms of N removal via denitrification processes, natural regeneration is a priority approach to restoring degraded riparian ecosystems. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Slamming is a complicated fluid–structure coupling process accompanied with complex transfer of load and energy, which may pose a significant risk to the overall safety of structure. This paper aims to evaluate the dynamic response and elucidate the failure mechanism of composite‐metal sandwich structures under slamming impact. Firstly, a reliable numerical simulation process is established based on CEL method in ABAQUS/Explicit combining with a VUMAT subroutine, whose effectiveness is verified through the comparison with published experimental results. Subsequently, dynamic response of the sandwich structures is investigated considering the influence of slamming velocity and material constituent. Meanwhile, damage evolution and critical failure mechanism are assessed through progressive damage analysis. Results show that CF‐Al‐CF case owns the best mechanical performance and the latest ultimate failure moment. The overall performance of sandwich structure is mainly dependent on the mechanical properties of skin. Additionally, damage of Al‐CF‐Al case is more sensitive to the variation of velocity compared with that of CF‐Al‐CF and Al‐Al‐Al cases, which indicates that the ductility of core is responsible for ultimate damage. Moreover, extensively distributed matrix tension damage can be identified as the critical damage mode, which may further cause debonding damage and even fiber fracture. [ABSTRACT FROM AUTHOR]

Aim: MATRICS Consensus Cognitive Battery was developed by the National Institute of Mental Health to establish acceptance criteria for measuring cognitive changes in schizophrenia and can be used to assess cognitive functions in other psychiatric disorders. We used a Japanese version of MATRICS Consensus Cognitive Battery to explore the changes in multiple cognitive functions in patients with mild cognitive impairment and mild Alzheimer's disease. Methods: We administered the Japanese version of MATRICS Consensus Cognitive Battery to 11 patients with mild cognitive impairment (MCI), 11 patients with Alzheimer's disease, and 27 healthy controls. All Japanese versions of MATRICS Consensus Cognitive Battery domain scores were converted to t‐scores using sample means and standard deviations and were compared for significant performance differences among healthy control, MCI, and mild Alzheimer's disease groups. Results: Compared with healthy controls, patients with MCI and mild Alzheimer's disease demonstrated the same degree of impairment to processing speed, verbal learning, and visual learning. Reasoning and problem‐solving showed significant impairments only in mild Alzheimer's disease. Verbal and visual abilities in working memory showed different performances in the MCI and mild Alzheimer's disease groups, with the Alzheimer's disease group demonstrating significantly more deficits in these domains. No significant difference was found among the groups in attention/vigilance and social cognition. Conclusions: The Japanese version of MATRICS Consensus Cognitive Battery can be used to elucidate the characteristics of cognitive dysfunction of normal aging, MCI, and mild dementia in clinical practice. [ABSTRACT FROM AUTHOR]

Lignin condensation reactions are hard to avoid or control during separation, which is a deterrent to lignin isolation and post‐conversation, especially for the full utilization of lignocelluloses. Selective protection of β‐aryl ether linkages in the isolation process is crucial to lignin valorization. Herein, a two‐step acid/alkali separation method assisted with l‐cysteine for eucalyptus lignin separation is developed, and the isolated l‐cysteine lignins (LCLs) are comprehensively characterized by 2D NMR, 31P NMR, thioacidolysis, etc. Compared to the two‐step control treatment, a much higher β‐O‐4 content is preserved without reducing the separation efficiency assisted by l‐cysteine, which is also significantly higher than alkali lignin and kraft lignin. The results of hydrogenolysis show that LCLs generate a much higher monomer yield than that of control sample. Structural analysis of LCLs suggests that lignin condensation reaction, to some extent, is suppressed by adding l‐cysteine during the two‐step acid/alkali separation. Further, mechanistic studies using dimeric model compound reveals that l‐cysteine may be the α‐carbon protective agent in the two‐step separation. The role of l‐cysteine in the two‐step lignin isolation method provides novel insights to the selective fractionation of lignin from biomass, especially for the full valorization of lignocellulosic biomass. [ABSTRACT FROM AUTHOR]

In conventional n–i–p perovskite solar cells (PVSCs), electron donor (D)–acceptor (A) polymers have been found to be potential substitutes for doped spiro‐based small molecule hole‐transporting materials (HTMs) due to their excellent performance in hole mobility, film formability, and stability. Herein, a benzo[1,2‐b:4,5‐b′]dithiophene (BDT)‐benzodithiophene‐4,8‐dione (BDD) copolymer PBDB‐Cz is developed by employing carbazole as the conjugated side chain of BDT. PBDB‐O and PBDB‐T with alkoxy and thiophene as the side chain of BDT, respectively, are also synthesized and studied for comparison. The synergistic effect of the carbazole side chain and the BDT‐BDD backbone to promote hole transport properties is found in PBDB‐Cz. The carbazole side chain enhances both coplanarity and interaction of polymer chains, while simultaneously deepening energy levels and improving the hole mobility of the polymeric HTM. Consequently, PBDB‐Cz outperforms two counterparts, exhibiting a promising power conversion efficiency (PCE) of 22.06%. Notably, the PBDB‐Cz also improves the device stability, and the devices can retain more than 90% of their initial PCEs after being stored at ambient conditions for 100 days. To the best of the authors' knowledge, this is the first report to incorporate carbazole into D–A polymeric HTM by side chain engineering. [ABSTRACT FROM AUTHOR]

Magnetic nanoparticles have many advantages in medicine such as their use in non-invasive imaging as a Magnetic Particle Imaging (MPI) tracer or Magnetic Resonance Imaging contrast agent, the ability to be externally shifted or actuated and externally excited to generate heat or release drugs for therapy. Existing nanoparticles have a gentle sigmoidal magnetization response that limits resolution and sensitivity. Here it is shown that super ferromagnetic iron oxide nanoparticle chains (SFMIOs) achieve an ideal step-like magnetization response to improve both image resolution & SNR by more than tenfold over conventional MPI. The underlying mechanism relies on dynamic magnetization with square-like hysteresis loops in response to 20 kHz, 15 kAm−1 MPI excitation, with nanoparticles assembling into a chain under an applied magnetic field. Experimental data shows a “1D avalanche” dipole reversal of every nanoparticle in the chain when the applied field overcomes the dynamic coercive threshold of dipole-dipole fields from adjacent nanoparticles in the chain. Intense inductive signal is produced from this event resulting in a sharp signal peak. Novel MPI imaging strategies are demonstrated to harness this behavior towards order-of-magnitude medical image improvements. SFMIOs can provide a breakthrough in noninvasive imaging of cancer, pulmonary embolism, gastrointestinal bleeds, stroke, and inflammation imaging. [ABSTRACT FROM AUTHOR]

Whether adding carboplatin to standard neoadjuvant chemotherapy improves survival in BRCA1/2‐mutated triple‐negative breast cancer (TNBC) is unknown. In this retrospective study, we aimed to explore the efficacy of anthracycline‐taxane (A‐T)‐based or anthracycline‐taxane/carboplatin (A‐TP)‐based neoadjuvant chemotherapy in BRCA1/2‐mutated TNBC. A total of 1585 operable primary breast cancer patients were treated with either neoadjuvant A‐T (n = 886) or A‐TP regimen (n = 699). BRCA1 and BRCA2 germline mutations were determined in all subjects. Pathological complete response (pCR), recurrence‐free survival (RFS), distant recurrence‐free survival (DRFS) and overall survival (OS) were estimated. Of the entire cohort, 102 patients (6.4%) carried a pathogenic BRCA1/2 germline mutation. After a median follow‐up of 81 months, no significant differences in survival between the A‐T and A‐TP arms were found in the entire cohort. However, among 288 TNBC patients, BRCA1/2 mutation carriers had significantly better survival when treated with the A‐TP regimen than with the A‐T regimen (5‐year RFS: 82.6% vs 47.9%; P =.024; 5‐year DRFS: 88.5% vs 46.9%; P =.010; 5‐year OS: 88.2% vs 49.9%; P =.036). Multivariate analyses revealed that the A‐TP regimen was a significantly favourable factor for RFS and DRFS and showed a trend towards better OS when compared with the A‐T regimen in BRCA1/2‐mutated TNBC (RFS: adjusted hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.06‐0.91, P =.035; DRFS: HR, 0.17; 95% CI, 0.03‐0.80; P =.025; OS: HR, 0.29; 95% CI, 0.06‐1.49; P =.14). Our study suggested that BRCA1/2‐mutated TNBC patients gain a survival benefit when carboplatin is added to standard A‐T‐based neoadjuvant chemotherapy. What's new? Due to their deficiency in DNA‐repair capacity, BRCA1/2 mutation carriers might be sensitive to platinum agents. Whether adding carboplatin to standard neoadjuvant chemotherapy improves survival in BRCA1/2‐mutated triple‐negative breast cancer however remains unknown. In this retrospective study, 1585 operable primary breast cancer patients were treated with either an anthracycline followed by taxane (A‐T) or an anthracycline followed by taxane plus carboplatin (A‐TP) neoadjuvant regimen. No significant differences in survival between the A‐T and A‐TP arms were found in the entire cohort. However, BRCA1/2‐mutated triple‐negative breast cancer patients showed significantly better survival with the A‐TP regimen than with the A‐T regimen. [ABSTRACT FROM AUTHOR]

The purpose of this article is to investigate the mechanical responses and critical failure mechanisms of notched composite laminates with the aid of numerical and experimental approaches, considering the effect of notch geometry, notch size and off‐axis angle. Quasi‐static tensile tests are implemented to study the influence of design variables on the mechanical response, during which the relationship of force vs displacement and strain distributions are collected by means of digital image correlation technique. Subsequently, the numerical simulation is implemented in ABAQUS/Explicit through a progressive damage model integrated with a VUMAT subroutine. Meanwhile, the initiation and propagation of damage are explored through the damage morphologies, combining with the logarithmic strain components from numerical predictions. Results show that notch strength and failure strain are more closely associated with off‐axis angle and notch size compared with notch geometry. In addition, with the increase of off‐axis angle, the contribution of fiber is increasingly weakened, the damage mode gradually varies from fiber fracture to pull out accompanied with the damage near the notch changing from fiber fracture to delamination. Meanwhile, the critical failure mechanism varies from tension dominated to tension‐shear/shear dominated as the off‐axis angle grows larger. [ABSTRACT FROM AUTHOR]

Objectives: Long‐tailed macaques (Macaca fascicularis) are widely distributed throughout the mainland and islands of Southeast Asia, making them a useful model for understanding the complex biogeographical history resulting from drastic changes in sea levels throughout the Pleistocene. Past studies based on mitochondrial genomes (mitogenomes) of long‐tailed macaque museum specimens have traced their colonization patterns throughout the archipelago, but mitogenomes trace only the maternal history. Here, our objectives were to trace phylogeographic patterns of long‐tailed macaques using low‐coverage nuclear DNA (nDNA) data from museum specimens. Methods: We performed population genetic analyses and phylogenetic reconstruction on nuclear single nucleotide polymorphisms (SNPs) from shotgun sequencing of 75 long‐tailed macaque museum specimens from localities throughout Southeast Asia. Results: We show that shotgun sequencing of museum specimens yields sufficient genome coverage (average ~1.7%) for reconstructing population relationships using SNP data. Contrary to expectations of divergent results between nuclear and mitochondrial genomes for a female philopatric species, phylogeographical patterns based on nuclear SNPs proved to be closely similar to those found using mitogenomes. In particular, population genetic analyses and phylogenetic reconstruction from the nDNA identify two major clades within M. fascicularis: Clade A includes all individuals from the mainland along with individuals from northern Sumatra, while Clade B consists of the remaining island‐living individuals, including those from southern Sumatra. Conclusions: Overall, we demonstrate that low‐coverage sequencing of nDNA from museum specimens provides enough data for examining broad phylogeographic patterns, although greater genome coverage and sequencing depth would be needed to distinguish between very closely related populations, such as those throughout the Philippines. [ABSTRACT FROM AUTHOR]

In this study, the effect of different zinc salts (ZnCl2 and ZnSO4) on the deactivation of activated carbon(AC)‐based Mn−Ce catalysts and the poisoning mechanism of zinc salts on Mn−Ce/AC are comparatively studied. SEM, BET, XRD, XPS, H2‐TPR, NH3‐TPD and In‐situ DRIFT are used to characterize the physical and chemical changes of Mn−Ce/AC catalyst. The Selective Catalytic Reduction (SCR) activities of Mn−Ce/AC has a noticeable decline after loading zinc salts, and the highest NO conversion of Zn poisoning catalysts do not exceed 70 %. And the acid site is occupied by Zn2+ on the catalyst, which affects the chemical adsorption of NH3 and hinders the formation of the intermediate ‐NH2. Moreover, the decrease of Mn4+, reducibility of manganese oxide and acid sites are more serious on ZnC−Mn‐Ce/AC. Besides, loading ZnSO4 can improve the content of Ce3+ and Oβ on catalyst surface, which can mitigate the poisoning effects of ZnSO4 on Mn−Ce/AC catalyst. Hence, ZnCl2 displays a more serious poisoning effect on Mn−Ce/AC catalyst compared with ZnSO4. Then the probable mechanism model of ZnCl2 and ZnSO4 on Mn−Ce /AC catalyst is proposed and compared. [ABSTRACT FROM AUTHOR]

The spectrum and frequency of BRCA1/2 pathogenic variants may be ethnicity‐specific. Whether high‐frequency founder mutations are present in Chinese women remains largely unknown. In the current study, germline pathogenic variants in the BRCA1/2 genes were determined in 9,505 unselected Chinese Han breast cancer (BC) patients by next‐generation and/ or Sanger sequencing. Four hundred and seventy‐one (5.0%) BC patients carried BRCA1/2 pathogenic variants in this cohort. A total of 25 recurrent pathogenic variants (at least found in four unrelated patients) were identified in this cohort (8 BRCA1 and 17 BRCA2 recurrent pathogenic variants), 161 patients carried one of these recurrent pathogenic variants in this cohort of 9,505 patients. All of these 25 recurrent pathogenic variants were further explored whether they had founder effect through haplotype analysis. The most common pathogenic variant, BRCA1 c.5470_5477del, was found in 30 BC patients from 29 unrelated families. Twenty‐seven of these 29 unrelated patients who carried this BRCA1 c.5470_5477del mutation shared an identical haplotype, indicating that BRCA1 c.5470_5477del was a founder mutation in the Chinese Han population. Furthermore, BRCA1 c.5470_5477del mutation carriers had a significantly worse survival than noncarriers (disease‐free survival, p = 0.049; overall survival, p = 0.029). Taken together, our data suggested that BRCA1 c.5470_5477del is a founder mutation in the Chinese Han population and BRCA1 c.5470_5477del mutation carriers have a poor survival. What's new? Founder mutations in the BRCA1/2 genes are mostly defined in Caucasian populations while other ethnicities remain understudied. Here the authors studied a new gene variant in almost 10,000 Chinese Han women with breast cancer. The BRCA1 c.5470_5477del variant was found in 0.3% of the women in the study, most of them sharing the same haplotype, suggesting that it functions as a new founder mutation in this ethnic population. [ABSTRACT FROM AUTHOR]

Background: Achalasia is an esophageal motility disorder with unknown etiology. Previous findings indicate that immune‐mediated inflammatory process causes inhibitory neuronal degeneration. This study was designed to evaluate levels of serological cytokines and chemokines in patients with achalasia. Methods: We collected information from forty‐seven patients with achalasia who underwent peroral endoscopic myotomy. Control samples were collected from forty‐seven age‐ and sex‐matched healthy people. The concentrations of serological cytokines and chemokines were analyzed by Luminex xMAP immunoassay. Serological and clinical data were compared between groups. Key Results: Compared with healthy controls, achalasia patients had significantly increased concentrations of eleven cytokines and chemokines, namely, TGF‐ß1 (P <.001), TGF‐ß2 (P <.001), TGF‐ß3 (P <.001), IL‐1ra (P <.001), IL‐17 (P =.005), IL‐18 (P <.001), IFN‐γ (P <.001), MIG (P <.001), PDGF‐BB (P <.001), IP‐10 (P =.003), and SCGF‐B (P <.001). Gene ontology (GO) and network functional enrichment analysis revealed regulation of signaling receptor activity and receptor‐ligand activity were the most related pathways of these cytokines and chemokines. Levels of twelve cytokines and chemokines were significantly increased in type III compared with I/II achalasia, namely, TGF‐ß2, IL‐1ra, IL‐2Ra, IL‐18, MIG, IFN‐γ, SDF‐1a, Eotaxin, PDGF‐BB, IP‐10, MCP‐1, and TRAIL. Conclusions and Inferences: Patients with achalasia exhibited increased levels of serological cytokines and chemokines. Levels of cytokines and chemokines were significantly increased in type III than in type I/II achalasia. Cytokines and chemokines might contribute to the inflammatory development of achalasia. [ABSTRACT FROM AUTHOR]

Biodiesel is a clean energy source that helps in the reduction of environmental pollution as compared to fossil fuel. This study aimed to improve the performance of combustion and reduce emission in direct injection rotary engine by fueling it with biodiesel as well as selecting the best ignition time. A 3D‐dynamic simulation model was established and then coupled with biodiesel chemical kinetics mechanism. On this basis, investigation of five ignition timings (IT) was conducted to know their various effects on combustion process. The simulation results showed that properly advancing IT increased in‐cylinder pressure, with the peak pressure (Pmax) of 35°CA (BTDC) IT of 45.99 bar the largest. Comparing IT of 35°CA (BTDC) with the IT of the original engine showed an 18.14% increase in peak pressure. The corresponding crank angle (φmax) for Pmax values also proved that when the IT was advanced, φmax values decreased and that of 35°CA (BTDC)‐10.37°CA (ATDC), 30°CA (BTDC)‐11.46°CA (ATDC), and 25°CA (BTDC)‐13.88°CA (ATDC) were better because they were generally between 10–15°CA (ATDC), which contributes to better engine performance. With advanced IT, phase of total period during combustion was continuously brought forward due to flame propagation acceleration by tumble as well as increase of tumble residence effect time that aided in improving the combustion rate. The burnt fuel mass fractions at TDC of 40°CA (BTDC) IT of 0.94 was the highest followed by 35°CA (BTDC) IT of 0.88. Under this computational condition, 35°CA (BTDC) was deemed to be the improved combustion scheme though soot exhaust increased. [ABSTRACT FROM AUTHOR]

Objective: With the discovery of thermogenic adipocytes in humans, it has been hypothesized that enhancing adaptive thermogenesis may improve obesity. Although many studies have found that ginseng can improve obesity, the beneficial effects of ginsenoside Rd on obesity and its mechanisms have not been studied.Methods: High-fat diet-induced obese mice were used as the study subjects, with intraperitoneal injection of Rd daily at a dose of 15 mg/kg. Body weight and energy metabolism were observed. The effects of Rd on glucose tolerance, insulin sensitivity, and cold tolerance were tested. The expression of genes associated with thermogenesis was analyzed. Finally, the mechanisms by which Rd regulates adaptive thermogenesis were studied.Results: Rd ameliorated obesity and insulin resistance. Rd increased cold tolerance through enhancing thermogenic gene expression in brown adipose tissue and increased the browning of white adipose tissue induced by cold stress. Rd increased intracellular cyclic adenosine monophosphate (cAMP) content. Decreasing intracellular cAMP levels by an inhibitor of adenylyl cyclase SQ22536 abolished the promoting effects of Rd on the expression of thermogenic genes.Conclusions: Rd improves obesity and insulin resistance. The upregulation of thermogenesis by Rd is dependent on the cAMP/protein kinase A signaling pathway. [ABSTRACT FROM AUTHOR]

The prevalence and clinical relevance of TP53 germline mutations in a large unselected breast cancer series are largely unknown. Here, we determined TP53 germline mutations in a large cohort of 10,053 unselected breast cancer patients through multigene panel‐based next‐generation and/or Sanger sequencing assays. We found that 0.5% of patients (50 cases) carried a pathogenic TP53 germline mutation in this large series of 10,053 unselected breast cancer patients, and the prevalence of TP53 germline mutation was 3.8% in very early onset breast cancer (age ≤30 years) in this large cohort. TP53 mutation carriers were significantly more likely to have early onset cancer (p < 0.001) and bilateral breast cancer (p = 0.03), they and were significantly more likely to respond to carboplatin‐based neoadjuvant chemotherapy compared to anthracycline‐ or taxane‐based regimen in terms of pathologic complete response (50% vs. 0%, p = 0.006). At the median follow‐up of 54 months, TP53 mutation was an independent unfavorable factor for recurrence‐free survival (RFS), distant recurrence‐free survival (DRFS), and overall survival (OS) (RFS, adjusted hazard ratio [HR]: 2.24, 95% confidence interval [CI]: 1.15–4.33, p = 0.02; DRFS, adjusted HR: 2.73, 95% CI: 1.41–5.30, p = 0.003; OS, adjusted HR: 4.60, 95% CI: 2.26–9.41, p < 0.001) in multivariate analyses. Our study suggested that TP53 germline mutations occur more frequently in very early onset unselected breast cancer patients; and TP53 germline mutation carriers have a very poor survival and may benefit from carboplatin‐based neoadjuvant chemotherapy in unselected breast cancer patients. What's new? Carriers of germline mutations of the tumor suppressor TP53 have a 100‐times higher risk to develop cancer, often in multiple organs, but the clinical relevance of the mutations in women with breast cancer remains unclear. Here, the authors examined more than 10,000 Chinese women with breast cancer and found 0.5% (50 cases) carried a pathogenic TP53 germline mutation. Carriers more often had early‐onset disease, a poorer survival and responded to carboplatin‐based neoadjuvant chemotherapy, the latter a relevant therapeutic outcome of testing for mutation carriers. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The purpose of the present study was to observe the relationship between serum α‐klotho (KL) protein level and diabetic retinopathy (DR), and to further examine the effects of KL protein on apoptosis induced by palmitic acid (PA) in human retinal endothelial cells. Materials and Methods: A total of 17 healthy people and 60 type 2 diabetes patients were included. According to the results from fundus fluorescein angiography, the diabetes patients were divided into three subgroups: without DR, non‐proliferative DR and proliferative DR. Serum KL level was measured by enzyme‐linked immunosorbent assay. In vitro, human retinal endothelial cells were exposed to PA with or without KL protein. Apoptosis rates were analyzed by flow cytometry analysis. Apoptotic‐related protein expressions were detected by western blotting analysis. Results: Serum KL level was lower in diabetes patients than that in healthy participants (P = 0.007), and was gradually decreased among the without DR, non‐proliferative DR and proliferative DR subgroups (P = 0.045). A logistic regression analysis showed that after adjusting for the other confounding factors, serum KL level was independently and negatively related with DR (P = 0.049). Furthermore, the increased apoptosis rates induced by PA were inhibited with the addition of KL protein. Consistently, KL protein reversed the expression levels of the increased pro‐apoptotic protein Bax and the decreased anti‐apoptotic protein Bcl‐2 induced by PA. However, the anti‐apoptotic effect of KL protein was attenuated by LY294002 through the phosphatidylinositol 3 kinase‐serine∕threonine kinase pathway. Conclusions: The data suggested that KL protein was probably a potential protective factor against retinopathy in type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

Aim: There is no consensus regarding the association between hormone replacement therapy (HRT) and risk of meningioma so far. We conducted the first study among Chinese female patients to investigate the influence of HRT use on the risk of meningioma. Methods: We retrospectively collected records of diagnosis of meningioma for women aged 50 years and above during 2011–2016 and dispense of HRT prior to meningioma diagnosis in three tertiary hospitals in China. Meningioma cases were matched with controls at a ratio of 1:2 by using nearest neighbor propensity scores matching in order to balance the baseline characteristics between groups, which generated a total of 629 cases with 1258 controls. Results: We observed prior use of HRT associated with increased risk of meningioma (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.0–1.4) and the association was more prominent among women having multiple HRT dispenses and longer term exposure (OR, 1.3; 95% CI, 1.1–1.6), among those with combination therapy of estrogens and progestogens (OR, 1.3; 95% CI, 1.1–1.7) than monotherapy, and among progestogen users than estrogen users as for monotherapy. Furthermore, vaginal, subcutaneous implant seems to be associated with a higher risk of meningioma compared with oral administration although no significance had been reached. Conclusion: This case–control study provides evidence that hormone use for an HRT purpose might constitute the development and growth of meningioma as an independent risk factor, especially for combination therapy and/or long‐term users, which supports that meningioma might be a hormone‐sensitive tumor. [ABSTRACT FROM AUTHOR]

With the creation of long‐lived defect states‐related donor‐acceptor pair (DAP) recombination pathway, the Zn doped CuInS2 quantum dots (CIZS QDs) sensitized TiO2 photoelectrode displayed a good photocurrent response ability with a density of 2.7 mA/cm2. Further introduction Au nanoparticles (NPs) between CIZS and TiO2, and the outermost layer CdS, the photocurrent of CdS‐CIZS−Au‐TiO2 reached 7.5 mA/cm2 with an increase of 75% and 175%, respectively. The enhancements both in photo‐conversion ability and photoelectrochemical hydrogen generation reactivity can be mainly attributed to the functions of Au NPs acting as electron traps to help separate the long‐lived carriers of CIZS QDs and subsequently improve interfacial charge transfer, as well as CdS's ability to enhance holes extraction. [ABSTRACT FROM AUTHOR]

A simple way for N‐doped porous carbon materials (ANCs) was prepared in N2 atmosphere through the KOH‐assisted carbonization of commercial melamine foam (MF) attached glucose. Adding glucose and KOH activation process have great effects on improving the electrochemical properties of ANCs materials. Compared with other materials, the optimal ANCs‐800, which is obtained with a KOH/glucose/MF weight ratio of 5:20:1 at 800 °C, exhibits the best capacitance performance with the specific surface area (SSA) of 1481 m2 g−1 and high nitrogen content of 3.7 at. %. It possesses prominent specific capacitance (387 F g−1 at 0.5 A g−1) and excellent cycling stability (98.6% retention after 10,000 cycles). Furthermore, in the symmetric supercapacitor, the ANCs‐800 electrode material maintains high energy density (24.2 W h kg−1 at 701.07 W kg−1) and great cycling performance (96.3% after 10,000 cycles). Accordingly, the facile synthetic approach and attractive electrochemical properties make ANCs‐800 a popular capacitor material. The N‐doped porous carbon materials (ANCs) were prepared by one‐pot method using melamine foam as skeleton and nitrogen source and glucose as carbon source. These materials present good electrochemical performance, and ANCs‐800 possesses prominent specific capacitance (387 F g−1 at 0.5 A g−1) and excellent cycling stability (98.6% retention after 10,000 cycles). [ABSTRACT FROM AUTHOR]

We have developed a 7.5 inch micro LED device based on LTPS, the resolution is 320RGB × 240. The VSR driving circuits, demux circuits, ESD circuits were well‐distributed in AA combining with side bonding process, finally, we produced a 0mm border micro LED device. The VSR signal, PVDD and PVEE signal were well placed in panel in order to reduce the mura problem. We saved some extra space for edging to narrow border to negative value by adjusting AA circumference devices. Then the micro LED panel can be Seamless splicing while the pixel pitch seems continuous in spite of the Seam. Due to seamless splicing and the borderless features, we can assemble various size and resolution devices. The micro LED size is 85µm × 150µm and the luminance can reach beyond 600nit. [ABSTRACT FROM AUTHOR]

Coseismic fault displacement is quite large at shallow depths in some earthquakes, and it implies that fault gouges and sediments have extremely low dynamic friction during seismic slip. However, the dynamic weakening mechanisms of gouges under wet conditions are still not well constrained. Here we present direct evidence for the occurrence of flash heating and local fluid pressurization in water‐saturated gouges, by performing low‐ to high‐velocity (V = 10 μm/s to 1 m/s) friction experiments in a pressure vessel, under conditions specially designed to suppress weakening effects of bulk thermal and compaction‐induced pressurization. The tested gouges exhibit transition from velocity strengthening to drastic velocity weakening as slip rates increase. Strong dynamic weakening starts to occur at V ≥ 0.04 m/s at the initiation of sliding (<~0.1 m), which is much more efficient than previously reported in terms of the weakening velocity and distance. Furthermore, the onset of weakening is always accompanied by an instantaneous dilatancy (10–25 μm), which is much larger than that observed in dry tests and in contrast with gradual changes displayed in the wet tests without dynamic weakening. Numerical modeling integrated with microstructural observation reveals that bulk thermal pressurization cannot explain the experimental results, while flash weakening triggered by vaporization of water layers on/around asperity contacts and the resultant local fluid pressurization may be responsible for the observed rapid weakening concomitant with instantaneous dilatancy. Given high efficiency of such weakening process, fluid‐infiltrated faults could be weakened more rapidly than previously recognized during seismic slip. Key Points: Dynamic weakening of wet gouges occurs at slip rates ≥40 mm/s at the onset of slip under conditions suppressing bulk fluid pressurizationThe onset of dynamic weakening is always contemporaneous with instantaneous dilatancyFlash weakening triggered by water vaporization around asperities and the resultant local pressurization may cause rapid dynamic weakening [ABSTRACT FROM AUTHOR]

Abstract: Aims/Introduction: To detect serum adipsin levels in individuals with different glucose tolerance, and investigate the relationship between adipsisn and the first phase of insulin secretion. Materials and Methods: A total of 56 patients with newly diagnosed type 2 diabetes mellitus, 36 patients with impaired glucose tolerance (IGT) and 45 individuals with normal glucose tolerance were enrolled. Intravenous glucose tolerance tests were carried out to evaluate pancreatic β‐cell function. The serum levels of adipsin, interleukin‐1β and high‐sensitivity C‐reactive protein were assayed. Results: Serum adipsin levels were significantly lower in the type 2 diabetes mellitus and the IGT patients than those in the normal glucose tolerance group (P < 0.05). The acute insulin response and area under the curve showed a progressive decrease in the normal glucose tolerance and IGT groups, and decreased to the lowest levels in the type 2 diabetes mellitus group (P < 0.05). Adipsin was found to be negatively correlated with waist‐to‐hip ratio, free fatty acid, fasting plasma glucose, 2‐h postprandial plasma glucose, glycated hemoglobin, homeostasis model assessment of insulin resistance, interleukin‐1β and high‐sensitivity C‐reactive protein (P < 0.05 or P < 0.001), and positively correlated with homeostasis model assessment of β‐cell function, high‐density lipoprotein cholesterol, the area under the curve of the first phase insulin secretion and acute insulin response (P < 0.05 or P < 0.001). Stepwise multiple regression analysis showed that homeostasis model assessment for β‐cell function and acute insulin response were independently related to adipsin (P < 0.05). Conclusions: Serum adipsin levels were lower in type 2 diabetes mellitus and IGT patients, and correlated with the first phase of insulin secretion. Adipsin might be involved in the pathology of type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we reviewed the advances in ginsenoside biosynthesis and metabolic regulation. To begin with, the application of elicitors in the ginsenoside biosynthesis was discussed. Methyl jasmonate (MJ) and analogues have the best effect on accumulation of ginsenoside compared with other elicitors, and few biotic elicitors are applied in Panax genus plants tissue culture. In addition, so far, more than 40 genes encoding ginsenoside biosynthesis related enzymes have been cloned and identified from Panax genus, such as UDP‐glycosyltransferases (UGT) genes UDPG, UGTAE2, UGT94Q2, UGTPg100, and UGTPg1. However, the downstream pathway of the ginsenoside biosynthesis is still not clear. Moreover, some methods have been used to increase the expression of functional genes and ginsenoside content in the ginsenoside synthesis pathway, including elicitors, overexpression, RNAi, and transcription factors. The ginsenoside biosynthesis pathway should be revealed so that ginsenoside contents can be regulated. [ABSTRACT FROM AUTHOR]